The importance of aromatic amine derivatives, aromatic alcohol derivatives or aromatic thiol derivatives is well known in the chemical industry. Many derivatives of these compounds, particularly those employed in the field of fine chemicals such as medicines, agricultural chemicals, dyes, photographic materials, etc. have complicated structures, and efficient and highly selective synthesis methods thereof are in demand.
Among the aromatic amine derivatives, aniline derivatives are particularly important, and synthesis methods thereof are described in the literature in detail. For example, known synthesis methods include a method wherein the aniline derivative is synthesized by the nitration and reduction of a benzene derivative, a method wherein reduction is carried out after the diazo coupling of a phenol, a method wherein reduction is carried out after forming a nitroso compound of a phenol, a method wherein an aniline derivative is synthesized from an amine and a benzene derivative by aromatic nucleophilic substitution reaction, a method utilizing the rearrangement reaction of a benzoic acid amide derivative and a method utilizing the rearrangement reaction of an acetophenone oxime derivative.
Among the aromatic alcohols, phenol derivatives are most important. Many methods are known for synthesizing a phenol derivative including a method of alkali fusion of an arylsulfonic acid, a method utilizing the rearrangement reaction of an acylbenzene with a peracid, a method wherein a phenol derivative is synthesized from a halobenzene and a hydroxyl ion by an aromatic nucleophilic substitution reaction and a method using the solvolysis of a diazonium salt.
With regard to thiophenols, known synthesis methods include a method wherein a thiophenol is synthesized by the reaction of a halobenzene with hydrogen sulfide ion or functional equivalent thereof through an aromatic nucleophilic substitution reaction, a method using a reduction reaction of an arylsulfonyl halide and a method wherein after a sulfenyl halide is subjected to Friedel-Crafts reaction, a deblocking reaction is carried out by an appropriate method.
Among these reactions, reactions for introducing an amino group, a hydroxyl group or a mercapto group by utilizing an aromatic nucleophilic substitution reaction are often used, because the reactions are generally applicable to aromatic rings having relatively complicated substituent groups. In these reactions, an amine is used when an amino group is introduced, a hydroxyl ion is used when a hydroxyl group is introduced, and a hydrogen sulfide ion is used when a mercapto group is introduced.
However, these reactions are generally carried out under basic conditions and must sometimes be carried out under severe reaction conditions such as under pressure. Hence, when functional groups such as an alkoxycarbonyl group, cyano group, etc. are present which are reactive under basic conditions, it is often necessary that these functional groups are previously protected or temporarily converted into other functional groups, or the reaction by nucleophilic substitution must be stopped.
In the case where two or more reaction sites exist, it is often difficult to selectively introduce a desired group into a desired position when an amine, hydroxyl ion or hydrogen sulfide ion is used.
For this reason, a protected amino group such as phthalimide, benzenesulfonamido group, etc. is used when an amino group is to be introduced. When a hydroxyl group is to be introduced, a protected hydroxyl group such as a carboxylic acid, e.g., acetic acid, or an alcohol such as methanol, etc. is used. When a mercapto group is to be introduced, a protected mercapto group such as xanthic acid, a thiourea, etc. is used.
However, a lowering in pKa particularly results when the protected amino group or the protected hydroxyl group is used to introduce an amino group or a hydroxyl group by the above described method, and in some circumstances, more severe reaction conditions are required. Accordingly, problems are still encountered when functional groups are present which can not withstand the above described basic conditions or which react with the protected amino groups or the protected hydroxyl groups, which protected groups are nucleophilic reagents.
Accordingly, a method has been desired for introducing the above described functional groups under reaction conditions which are as mild as possible.